Genetic Diseases Steal Too Many Kids' Futures. It Doesn't Have To Be This Way

Editor's Note: This piece is published in collaboration with WBUR's "BioBoom," a series about what the booming biotech industry means for greater Boston and beyond. You can explore the full series here. 

I want to live in a world where children have never heard of hemophilia or cystic fibrosis, because we have all but eradicated those diseases.

This isn’t a dream. The biotech industry is beginning to explore how we might impact genetic and metabolic diseases, by decisively intervening at birth with genetic therapies capable of lifelong transformation.

The Orphan Drug Act, enacted in 1983, gives incentives for biotech and pharmaceutical companies to develop drugs for rare diseases, sometimes known as “orphan” diseases. The incentives have done wonders, spurring the development and approval of hundreds of new therapeutics. But the vast majority of those drugs are for adults.

Prior to 2000, fewer than 10 percent of Orphan Drug Act approvals were for pediatric therapies. In the last two decades, that percentage has gone up, but even so, fewer than 25 percent of approved orphan drugs are designated for use in children, and just a fraction of those are approved for use in infants.

I see the greatest therapeutic opportunity -- and the most heart-wrenching unmet need -- in children living with rare genetic diseases.

I believe this ratio is backwards. As a pediatrician, I see the greatest therapeutic opportunity — and the most heart-wrenching unmet need — in children living with rare genetic diseases.

As an industry, we need to invest more in developing therapeutics for childhood diseases, ideally ones that can be given before symptoms arise. We need coordinated action by the private and the public sector — and a renewed will to tackle the genetic diseases that steal the future from too many kids.

Consider spinal muscular atrophy, or SMA, a brutal neuromuscular genetic disease which causes infants to progressively lose motor functions such as the ability to swallow, walk and breathe independently. There are about 9,000 patients in the U.S. with the disease, an incidence roughly on par with cystic fibrosis and ALS.

A drug for SMA, called Spinraza, was investigated initially in symptomatic infants by Biogen. The results were remarkable --- 51 percent of Spinraza-treated patients (versus 0 percent of patients who received the placebo) gained motor milestones. The babies who’d received Spinraza could feed normally, sit unassisted, rise to a stand and take a few steps. But, eventually, their progress plateaued.

For this reason, Spinraza was also tested in children who were pre-symptomatic. A diagnostic test, developed from a dried blood spot, was used to screen children for the disease. Those who tested positive were offered Spinraza prior to the onset of symptoms. Ultimately, 18 pre-symptomatic SMA infants were treated. Years later, none of those children have developed the devastating consequences of SMA. Today they are running and playing, just like normal, healthy children. Their families have barely experienced SMA, save for receiving medication via injection a few times a year.

What does the Spinraza story tell us?

It suggests that children — and especially, infants — are better candidates for up-and-coming therapeutics that use technology like genetic medicines, which seek to treat diseases caused by mutations in a patient’s cells.  Children’s bodies have a plasticity and repair capacity that does not exist in adults. And they stand to benefit immensely if we can treat their diseases early, before their bodies and minds suffer irreversible damage.

Importantly, we also need to develop new regulatory frameworks that allow for novel clinical trial designs — like intervening with an experimental drug in an infant who carries the genetic code for a rare disease, even before the child develops symptoms. As the SMA example illustrates, it is possible to design and carry out such trials, but it’s rare. In part this is because it’s scary — and, yes, risky — to test drugs on newborns, but the inevitable decline associated with a progressive genetic disease demands action.

I want to make the ravages of inherited diseases feel as imaginary to the next generation as polio or smallpox feel to today’s children.

As taxpayers, we should push for increased investment in research — by both the public and the private sectors — to understand neonatal physiology and develop new screening tests that can identify genetic diseases even before symptoms arise.  We need to be sure these trials are informed by deep scientific understanding and a thoughtful analysis of the risks, the benefits and the ethics of such testing.

The biotech industry is developing approaches with the potential to dramatically change the fate of patients with genetic disease. If we can gather the tools — and the courage -- to implement these approaches during the neonatal period, we’ll see generations of children leading long and healthy lives, no longer impeded by their genetic legacy.

We have a model for how to do this. Modern vaccines have all but eliminated deadly infectious diseases like polio, smallpox and diphtheria. They have saved hundreds of millions of children worldwide from death or crippling disability.

Many of these vaccines were developed under conditions of extraordinary urgency. We had to stretch regulatory frameworks and develop new models for clinical trials to bring them onto the market quickly and safely. In recent decades, we saw a similar urgency lead to the development of anti-retroviral therapies that forever changed the outlook for people living with HIV.

I want to make the ravages of inherited diseases feel as imaginary to the next generation as polio or smallpox feel to today’s children. The key to achieving this — as it was with vaccines for infectious diseases — is to intervene before the onset of the disease results in irreversible consequences.

Doug Kerr, who leads preclinical research and clinical development at GenerationBio, contributed to the writing of this piece.